Project Summary The Bloomington Drosophila Stock Center (BDSC) supports a large, worldwide community of scientists using the insect Drosophila melanogaster as a model organism for biomedical experimentation. The goals of the BDSC are to provide a collection of documented living stocks of broad value to current research, to preserve documented strains with clear future value, and to provide information and support services that promote maximal exploitation of these materials. These goals facilitate research by providing universal and rapid access to the most generally useful stocks, by preserving specialty genotypes with exceptional characteristics, and by providing information that helps researchers identify stocks appropriate to their needs. Drosophila is used extensively in studies of biological processes relevant to human health and investigations of molecular mechanisms underlying disease, because genetic technologies available to Drosophila researchers are among the most sophisticated in any multicellular organism. As the most comprehensive source of stocks for genetic experimentation with Drosophila, the BDSC is central to the success of many research projects including a large number of NIH grants. The first specific aim of this proposal is to continue acquiring, maintaining and distributing Drosophila strains and to continue developing associated information resources to meet the research needs of Drosophila scientists while maintaining and promoting excellent user support. Key to this aim is the administration and advancement of the highly successful cost recovery program that finances operational expenses from user fees. Consequently, the proposal focuses on support and development of the core management team as the most effective way to leverage the investment of NIH resources. The second specific aim, which will comprise 10% of grant expenditures, is to undertake research to increase the utility of the two largest subsets of BDSC stocks. Stocks carrying GAL4 or split-GAL4 transgenes are used to force expression of other transgenes in cell-specific patterns, allowing investigators to manipulate cell characteristics experimentally in otherwise normal individuals. They form the bases of many experimental approaches in Drosophila and most Drosophila models of human disease mechanisms, and the research here aims to characterize their expression patterns in the intestine, the most useful model system for studying the cell proliferation dynamics of a self-renewing epithelial tissue. Stocks carrying transgenes capable of expressing double-stranded RNAs under the control of GAL4 or split-GAL4 transgenes are used to knock down expression of specific genes via RNA interference mechanisms. A large collection of these stocks has been generated and preliminarily characterized. The research proposed here, in collaboration with the Transgenic RNAi Project at Harvard University, will evaluate the efficacy of these stocks in greater depth.